With the NCF's (National CFIDS Foundation) research
moving ahead, I have elected to look at several topics that
will be up for discussion. In this column, I will be examining
the concept of persistent mumps infection. I will also be
taking a look at abnormal ion channel function in CFIDS/ME
as it relates to a potential persistent mumps-like infection
(ie. - Parainfluenza Virus-5 infection). Hopefully, the
reader will be able to see some of the basic framework that
is beginning to emerge as a result of dissecting this small
segment of the disease process.

Let's first take a scientific look at another rubulavirus
that is very familiar and recognizable to most people.
I am talking about the mumps virus. Much like Parainfluenza
Virus-5 that has been identified in patients with CFIDS/ME
[1,2,3,4], PIV-5 is classified as a rubulavirus as is
mumps. Both viruses are members of the larger parainfluenza
(paramyxovirus) family.
What prompted this writing? Well, to tell you the truth,
I ran across several excellent articles. The first two
cover persistent mumps infection [5,6]. These two articles
should help to reinforce certain fundamental concepts
that appear to characterize rubulaviruses - the association
of sodium channel alterations on cellular excitation and
their implication in neurologic disease. As you will see,
sodium channel targeting is a characteristic of mumps
virus infection. This has important implications as ciguatoxin-like
activity, reflective of sodium channel alterations, has
been previously found in patient blood samples. This work
was completed by Dr. Yoshitsugi Hokama and funded by the
NCF.

Among RNA viruses that are known to persist in the human
central nervous system (CNS), members of the parainfluenza
(paramyxovirus) family are the most prominent. Both the
measles virus as well as the mumps virus has been implicated
in chronic neurological disease associated with persistent
infections of the CNS. In fact, the mumps virus is the
single most common cause of meningitis and encephalitis.
However, various neurological symptoms, including ataxia
and psychological disorders, can follow acute infections
and have been reported to be associated with elevated
mumps virus antibody titers in the cerebrospinal fluid
years after the infection. The scientific literature suggests
that the long term effects of mumps virus infection could
be due to irreversible brain damage following acute infection
or to a chronic infectious process. Is this a far fetched
idea? Hardly. Other members of the parainfluenza family
cause persistent infections of the brain. Canine distemper
virus and the measles virus are examples here. Both of
these viruses persistently infect neural cells and therefore
alter their neural function. Years ago, I remember reading
in Hilary Johnson's acclaimed book, Osler's Web, the possibility
that CFIDS/ME was an infectious disease of the brain.
Well, let me now state that a persistent rubulavirus infection
that invades the CNS would certainly satisfy this observation!

Two researchers from the University of Minnesota's School
of Medicine have closely examined persistent mumps virus
infected cells. Dr. Richard Ziegler and Dr. Edward Stauffer
found that persistent infection by the mumps virus induced
alterations in cellular excitation. This cellular excitation
was due to alterations or changes in the sodium channels.
Ziegler and Stauffer found that such virus-altered action
potentials led to a disruption of normal synaptic transmission
in neural pathways affected by infected neurons. Thus,
normal integrative processes were affected and this led
to serious neurophysiological dysfunction.

Persistent mumps virus infection directly affects the
sodium channels but spares the calcium and potassium channels.
The authors concluded that "the viral effect is a
specific rather than a general one with the sodium channel
being particularly susceptible." What would cause
these types of changes in the sodium channel by the mumps
virus you might ask? The authors suggest that specific
viral proteins associated with the mumps virus itself
are directly responsible for this effect.
The NCF's previous research has shown that CFIDS/ME patients
have sodium channel alterations and that these alterations
are associated with cellular excitation. This knowledge
has come from the NCF's funded research efforts. Fortunately,
more research results are on the horizon.

Next, I want to examine a research paper written by Chaudhuri
et. al. in 2000 [7]. The title of this paper is "The
symptoms of chronic fatigue syndrome are related to abnormal
ion channel function." In this paper, the authors
explore the pathogenesis of chronic fatigue syndrome and
write "In the early 1960s, it was recognized that
nearly 5% of victims of acute ciguatera poisoning did
not recover for many months or years due to a chronic
disabling syndrome with persistent fatigability and weakness.
Chronic ciguatera poisoning is an important consideration
in the differential diagnosis of anyone presenting with
chronic fatigue or in whom the diagnosis of CFS is being
considered in certain parts of the world. Ciguatoxins
(CTXs) are heat stable, non-protein, lipophilic toxins
produced by a dinoflagellate (Gamberdiscus toxicus) associated
with dead coral and algae which can be passed up the food
chain to result in sporadic human outbreaks. They comprise
a group of unique heterocyclic molecules that include
some of the most potent ion-channel altering substances.
CTX-1 is the most potent sodium channel toxin known and
is the major toxin in ciguateric fish. CTX bind sodium
channel receptors in both somatic and autonomic nerves
in the open mode, producing a prolonged sodium channel
activation. Symptoms arise from the semi-permanent opening
of the sodium channels, explaining the phenomenon of paradoxical
temperature sensation, a sensation which is commonly reported
by most CFS patients. CTX also include a sleep-inducing
fraction (<1% of total toxicity) and hypersomnolence
is a typical symptom of ciguatoxicosis and CFS....CTX,
which can lead to CFS symptoms, block sodium channels
in the open mode causing entry of sodium into neural tissues
and muscles. This ingress of sodium is followed by water
which in turn, leads to swelling of neural tissues, a
phenomenon observed both electrons microscopically and
by laser scanning microscopy with volume measurements
calculated by three-dimensional volume reconstruction.
It is postulated that chronic effects of CTX at the molecular
and osmostic level (intracellular edema) can account for
at least some of the subjective symptoms of lethargy,
weakness and easy fatiguability. If this is correct, then
it follows that some of the symptoms of CFS might be due
to ion channel abnormalities involving neural and skeletal
muscle tissues." Chaudhuri et. al. state that "Circumstantial
evidence supports the concept of an acquired channelopathy
in CFS."

The NCF is of the opinion that the observations by Chaudhuri
et. al. are in agreement with the research generated by
Dr. Hokama who has provided evidence for the presence
of ciguatoxin-reactivity in patients with chronic fatigue
syndrome and whose function acts to alter the sodium channels
in this disease [8]. Furthermore, the evidence provided
herein supports the notion that rubulavirus infections
directly target the sodium channels through an interaction
with virus specific proteins. Preliminary research supports
the role for PIV-5 targeted sodium channel alterations
and therefore functions. Such changes, as outlined above,
are associated with the symptoms of CFIDS/ME.